Deterioration of bone microarchitecture in prediabetes is partly mediated through fibroblast growth factor 21

Abstract

Introduction: Prediabetes has been reported to be associated with a worse trabecular bone score (TBS). Fibroblast growth factor 21 (FGF21) levels are raised in prediabetes and other insulin-resistant states, and FGF21 has been reported to be implicated in bone metabolism. We compared the bone mineral density (BMD) and TBS between prediabetes and normoglycemia, and studied the correlation of FGF21 with BMD and TBS. Method: Chinese postmenopausal women aged between 55 and 80 and without type 2 diabetes were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study between November 2016 and October 2018. Participants were excluded if they were already on anti-osteoporosis therapy, had secondary causes of osteoporosis, had body mass index (BMI) <15 or >37 kg/m2 (when TBS measurement may not be accurate), or had an estimated glomerular filtration rate (eGFR) <30mL/min. They were divided into prediabetes (defined by fasting glucose ≥5.6mmol/L or HbA1c ≥5.7%) and normoglycemia. BMD and TBS were measured by dual-energy X-ray absorptiometry. Serum FGF21 levels were measured with an in-house ELISA kit. Results: 258 participants were included (130 prediabetes and 128 normoglycemia), with a mean age of 61.5±5.1years and mean BMI of 24.2±3.7kg/m2. BMD over lumbar spine, femoral neck and total hip were all comparable between prediabetes and normoglycaemia, while TBS was lower in prediabetes (1.27±0.07 vs 1.30±0.07, p=0.007), which remained significant after adjustment for age and BMI. Serum FGF21 levels did not correlate with BMD but inversely correlated with TBS. On multiple linear regression models, serum FGF21 levels showed an independent inverse correlation with TBS (standardized beta -0.13, p=0.031), which remained significant with the inclusion of homeostasis model assessment of insulin resistance (HOMA-IR) in the model. Conclusion: Among Chinese postmenopausal women, bone quality was worse in prediabetes despite comparable bone density. Serum FGF21 levels showed a significant independent correlation with TBS, suggesting the potential impact of FGF21 on the deterioration of the bone microarchitecture in prediabetes.